Metabolic health in short children born small for gestational age treated with growth hormone and gonadotropin-releasing hormone analog: Results of a randomized, dose-response trial

Abstract

Context: Previously we showed that pubertal children born small for gestational age (SGA) with a poor adult height (AH) expectation can benefit from treatment withGH1 mg/m2 per day (∼0.033 mg/kg/d) in combination with 2 years of GnRH analog (GnRHa) and even more so with a doubleGH dose. GnRHa treatment is thought to have negative effects on body composition and blood pressure. Long-term effects and GH-dose effectsonmetabolic health in children treated with combined GH/GnRHa are unknown. Objective: This study aimed to investigate body composition, blood pressure, and lipid profile during GH treatment, either with or without 2 years of additional GnRHa. To assess whether GH 2 mg/m2 per day (∼0.067 mg/kg/d) results in a similar or even more favorable metabolic health at AH than GH 1 mg/m2 per day. Methods: This was a longitudinal, randomized, dose-response GH trial involving 107 short SGA children (58 girls) treated with GH until AH (GH randomized 1 or 2 mg/m2/d during puberty). Sixty-four children received additional GnRHa. At AH, metabolic parameters were compared between children treated with combined GH/GnRHa and those with only GH. The GH dose effect on metabolic health was evaluated in a subgroup of 47 children who started GH treatment in early puberty (randomized 1 or 2 mg/m2/d) with 2 years of GnRHa. Results: At AH, fat mass percentage (FM%) SD score (SDS), lean body mass (LBM) SDS, blood pressure SDS, and lipid profile were similar between children treated with combined GH/GnRHa and those with only GH. In the pubertal subgroup, FM% SDS was lower during treatment with GH 2 mg/m2 per day. There was no GH dose-dependent effect on LBM SDS, blood pressure, and lipid profile. Conclusions: Combined GH/GnRHa treatment has no long-term negative effects on metabolic health compared with only GH. Started in early puberty, a GH dose of 2 mg/m2 per day results in a similar metabolic health at AH and a more favorable FM% than GH 1 mg/m2 per day.